We have developed highly specific antisera to the human receptor for epidermal growth factor (EGF). These antisera have been employed to determine directly factors affecting the metabolism of the receptor protein. We have demonstrated, for example, that incubation of cells with EGF leads to a 10-fold increase in the rate of degradation of the EGF receptor molecule. The EGF receptor, therefore, is somewhat unique in that internalization is followed by degradation and not recycling. Also, we have shown that antisera that block the binding of [unreadable]125[unreadable]I-EGF to its receptor inhibit the biological activities of sarcoma growth factor (SGF). The EGF receptor, therefore, is required for the activities of SGF that is thought to be related to the transformed state of tumor cells. Related studies have now shown that antisera to the EGF receptor blocks the activity of a factor in tumor cell media that stimulates bone resorption. This activity is thought to be related to the hypercalcemia that is often associated with malignancies. Recent studies have defined the characteristics of the EGF receptor that are associated with its biosynthesis. These data show that the EGF receptor in a non-glycosylated form is not able to either bind [unreadable]125[unreadable]I-EGF or demonstrate tyrosine kinase activity. Partially glycosylated receptor molecules, however, are fully functional. Both co-translational and post-translational steps seem to be important for the acquisition of biochemical properties in the EGF receptor molecule. (J)